Solid reagents

ABSTRACT

An object of the present invention is to provide a novel solid reagent capable of solving the problems of conventional solid reagents based on resin beads. 
     The present invention relates to a solid reagent comprising an organic polymer base in which a polymer side chain is introduced onto the backbone of the organic polymer base via graft polymerization and a reactive functional group is introduced onto the polymer side chain. The organic polymer base is preferably in the form of a fiber, a woven or nonwoven fabric consisting of an assembly of fibers, a porous membrane or a hollow fiber membrane. The graft polymerization is preferably a radiation-induced graft polymerization. Solid reagents according to the present invention can be used in various organic synthetic reactions.

BACKGROUND OF THE INVENTION

The present invention relates to so-called solid reagents (also referredto as polymer-bound reagents or polymer-supported reagents).

Many reagents used in various organic syntheses such as oxidizingagents, reducing agents, deprotonating agents, halogenating agents andnucleophilic displacing agents are hard to handle because of theirproperties such as toxicity, combustibility, volatility andcorrosiveness. They are sometimes poor in the yield or selectivity oftarget compounds. Moreover, common reagents are mixed with a startingmaterial in a solvent for a desired reaction so that they requirecomplex operations such as extraction, filtration, drying andpurification in order to remove unreacted reagents and by-products fromthe medium and to isolate only a target compound after the reaction, andmany of them have the problem that they generate a large volume ofwaste.

As one of means for solving or reducing these problems, solid reagentshave been developed in which a reactive functional group or a reagentcompound itself is immobilized on a carrier such as silica gel or apolymer resin.

Polymer resins have found a wide range of applications in chemicalsyntheses since Merrifield proposed application for peptide synthesis inthe 1970s. Among others, many reports proposed using polymer resins ascarriers for solid reagents, as introduced in reviews such as Angew.Chem. Int. Ed., 40, 650 (2001), Synthesis, No. 8, 1035 (2000).

The use of solid reagents in organic syntheses generally has thefollowing advantages. They are safer and easier to handle thanconventional equivalent reagents (liquid or gaseous reagents); targetcompounds can be obtained with high yield by excessively using suchreagents; and unreacted and reacted reagents and target compounds can bereadily separated by filtration after the reaction has been completed.Many of them further have the following advantages. Some kinds of solidreagents afford target compounds with higher selectivity thanconventional equivalent reagents; target compounds can be obtained onlyby passing a solution of a starting compound through a column packedwith a solid reagent; and solid reagents can be regenerated/reused. Itcan be said from these facts that processes using solid reagents areenvironment-conscious. Solid reagents may be used by passing a solutionof a starting compound through a bed of a solid reagent as describedabove or by passing a gas of a starting compound through a bed of asolid reagent, though the following description is limited to the modein which a solution is passed for convenience sake. However, solidreagents including those of the present invention naturally cover theapplication mode in which a raw material gas is passed and such a modeis also included in the scope of the present invention.

Some of these results have already been commercialized. For example,some of ion exchange resins commercially available under Amberlyst havebeen converted from salt forms to have functions as oxidizing agents,reducing agents, various halogenating agents or nitrating agents.Polymer resins other than ion exchange resins are also commerciallyavailable such as polystyrene resins supporting osmium tetraoxide thatwas previously difficult to handle (from Wako Pure Chemical Industries,Ltd.).

However, all these conventional solid reagents have the problem thatthey are liable to physical wear/strength reduction during use becausethey use polymer resins prepared with crosslinkers (crosslinkedpolymers) as carriers, which change in volume by swelling orcontraction.

Moreover, molecules of a starting compound and reactive functionalgroups or reagent compound molecules supported on a solid reagent mustcome into thorough contact with each other in order that a chemicalreaction may proceed, but conventional solid reagents generally useporous bead-like resins so that molecules of a starting compound must bediffused for access to reactive functional groups or reagent compoundmolecules supported on the inner surfaces of micropores of the porousresin beads in order that a desired chemical reaction may proceed, whichgreatly impedes smooth progress of the chemical reaction.

Furthermore, the starting material solution must be passed at anextremely slow flow rate, and therefore over a very long time whenconventional solid reagents are to be used in large-scale columnreactions. If the flow rate is increased in this case, the startingcompound cannot be sufficiently diffused into the interior side of resinbeads, which results in an extremely lowered utilization efficiency ofreactive functional groups or reagent compound molecules and therefore adecreased yield of the target compound.

The utilization efficiency of reactive functional groups or reagentcompound molecules may be increased by reducing the particle diameter ofresin beads or further increasing the surface area, but serious pressureloss (differential pressure) in large-scale reactor systems requiresconsiderable strength in reactors or pumps.

For the reasons described above, conventional solid reagents often hadfurther problems associated with regeneration of used reagents, such aslengthy regeneration procedures, need for large amounts of regenerantsand low regeneration efficiency.

Consequentially, very few solid reagents are actually used in industrialchemical processes because of the inevitable problem of the poor costperformance for use in industrial chemical processes despite great manyproposals of solid reagents as introduced in the review mentioned above.

Several means to solve the above problems were proposed from the aspectof hardware such as reaction vessel or reaction apparatus, but solidreagents optimized for synthetic procedures have been stillinsufficiently developed.

SUMMARY OF THE INVENTION

As a result of careful studies to develop a novel solid reagent capableof solving the problems of conventional solid reagents based on resinbeads, we found that a solid reagent with very excellent properties canbe obtained by forming a polymer side chain having a reactive functionalgroup on the backbone of a polymer base having no crosslinked structuresuch as a fiber or a woven or nonwoven fabric via graft polymerizationand finally accomplished the present invention.

Accordingly, the present invention relates to a solid reagent comprisinga polymer base in which a polymer side chain is introduced onto thebackbone of the organic polymer base via graft polymerization and areactive functional group is introduced onto the polymer side chain.

As used herein, the term “solid reagent” means such a reagent thatreacts stoichiometrically with a starting compound by contact with thestarting compound and is consumed along the progress of the reaction toundergo changes in functional groups and thus lose reactivity as areagent, but it can recover reactivity by restoring the functionalgroups with a regenerant as appropriate and it should be differentiatedfrom “solid catalysts” that themselves remain unchanged along theprogress of the reaction or “sustained-release drugs” that are designedto gradually release functional group moieties without contact with astarting compound as its reaction partner.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an example of a reactor according to the present invention.

FIG. 2 shows another example of a reactor according to the presentinvention.

FIG. 3 shows the concept of a multistage reactor according to anembodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Various aspects of the present invention are explained in detail below.

Organic polymer bases for forming solid reagents of the presentinvention are preferably polyolefin-based organic polymer bases.Polyolefin-based organic polymer bases are suitable for the purpose ofintroducing a graft side chain via radiation-induced graftpolymerization described below because they are not degradable byradiations. Specific examples of polyolefin-based polymer materials wellsuitable for use as organic polymer bases in the present inventioninclude, but not limited to, polyolefins such as polyethylene andpolypropylene; halogenated polyolefins such as PTFE and vinyl chloride;and olefin-halogenated olefin copolymers such as ethylene-ethylenetetrafluoride copolymers and ethylene-vinyl alcohol copolymers (EVA).These organic polymer bases can be preferably used in the form of afiber, a woven or nonwoven fabric consisting of an assembly of fibers, aporous membrane or a hollow fiber membrane or the like.

Solid reagents of the present invention have a polymer side chainintroduced onto the backbone of an organic polymer base as describedabove via graft polymerization and a reactive functional groupintroduced onto the polymer side chain. Radiation-induced graftpolymerization is preferably used in the present invention.Radiation-induced graft polymerization is a method that allows a desiredgraft polymer side chain to be introduced into an organic polymer baseby irradiating the base to produce radicals and reacting them with agraft monomer, and this method is most preferred for the purpose of thepresent invention because polymer side chains can be introduced intoexisting polymer materials in various shapes.

Radiations that can be used in radiation-induced graft polymerizationinclude α-rays, μ-rays, γ-rays, electron rays, UV ray, etc., among whichγ-rays and electron rays are well suitable for use in the presentinvention. Radiation-induced graft polymerization includespreirradiation graft polymerization involving preliminarily irradiatinga graft base and then bringing it into contact with a polymerizablemonomer (graft monomer) for reaction, and simultaneous irradiation graftpolymerization involving simultaneously irradiating a base and amonomer, and either method can be used in the present invention.Radiation-induced graft polymerization includes various manners ofcontact between a monomer and a base, such as liquid phase graftpolymerization performed with a base immersed in a monomer solution, gasphase graft polymerization performed with a base in contact with thevapor of a monomer, or immersion gas phase graft polymerizationperformed by immersing a base in a monomer solution and then removing itfrom the monomer solution for reaction in a gas phase, and any methodcan be used in the present invention.

As described above, fibers and woven/nonwoven fabrics consisting of anassembly of fibers are suitable materials for use as organic polymerbases for forming solid reagents of the present invention, and these arewell suitable for use in the immersion gas phase graft polymerizationbecause they tend to retain monomer solutions.

In the preparation of solid reagents of the present invention, apolymerizable monomer having a carbon-carbon double bond and having afunctional group capable of being converted into a reactive functionalgroup participating in a desired chemical reaction is used as a graftmonomer in a reaction for introducing a polymer side chain onto thebackbone of an organic polymer base (graft polymerization reaction).Such polymerizable monomers include e.g. styrene, chloromethylstyrene,4-vinylpyridine, acrylic acid, acrylonitrile, etc. Solid reagents of thepresent invention can be formed by graft-polymerizing such apolymerizable monomer onto the backbone of an organic polymer basepreferably via radiation-induced graft polymerization to form a sidechain and then converting the functional group on the polymer side chaininto a reactive functional group participating in a desired chemicalreaction by a known method. According to the present invention, solidreagents that can participate in reactions such as oxidation reactions,reduction reactions, deprotonation reactions, halogenation reactions andnucleophilic displacement reactions are provided.

Further, in the preparation of solid reagents of the present invention,a polymerizable monomer having a carbon-carbon double bond and having areactive functional group participating in a desired chemical reactionmay also be used as a graft monomer. In this case, the solid reagentshaving graft polymer side chain having a desired reactive functionalgroup on the backbone may be formed by graft-polymerizing such apolymerizable monomer onto the backbone of an organic polymer base.Polymerizable monomers which can be used in this purpose include e.g.4-vinylbenzyltrimethylammonium salt, etc.

The present invention also relates to processes for preparing solidreagents as described above. Accordingly, another aspect of the presentinvention relates to a process for preparing a solid reagent comprisinggraft-polymerizing a polymerizable monomer having a reactive functionalgroup onto the backbone of an organic polymer base to form a polymerside chain having the reactive functional group. The present inventionalso relates to a process for preparing a solid reagent, comprisinggraft-polymerizing a polymerizable monomer having a group capable ofbeing converted into a reactive functional group onto the backbone of anorganic polymer base to form a polymer side chain and then convertingthe group capable of being converted into a reactive functional group onthe polymer side chain into the reactive functional group. The graftpolymerization is preferably conducted via radiation-induced graftpolymerization.

In a specific embodiment of the process for preparing a solid reagentaccording to the present invention, solid reagents of the presentinvention serving as reagents for oxidation reactions can be formed bygraft-polymerizing chloromethylstyrene used as a polymerizable monomeronto an organic polymer base such as a polyethylene nonwoven fabric viaradiation-induced graft polymerization to form a polymer side chain,then immersing the base in a solution of a trialkylamine such astrimethylamine to introduce a quaternary ammonium-type anion exchangegroup onto the polymer side chain, and converting the anion intohypochlorite ion, periodate ion, peroxide ion, chromate ion, dichromateion, perruthenate ion, etc. Solid reagents of the present inventionserving as reagents for reduction reactions can be formed by convertinganion of the quaternary ammonium group introduced onto the polymer sidechain into tetrahydroborate ion, cyanotrihydroborate ion, etc.Alternatively, solid reagents of the present invention that canparticipate as deprotonating agents in condensation reactions such asaldol condensation, Claisen condensation and Dieckmann condensation orRobinson annellation reaction can be formed by converting the anion ofthe quaternary ammonium group into hydroxide ion or the like. Moreover,solid reagents of the present invention serving as halogenating agentssuch as brominating agents can be formed by converting the anion of thequaternary ammonium group into tribromide ion or the like, or solidreagents participating in nucleophilic displacement reactions such ascyanation, thiocyanation, azidation and nitration can be formed byconverting the anion of the quaternary ammonium group into cyanide ion,cyanate ion, thiocyanate ion, azide ion, nitrite ion, etc.

Alternatively, solid reagents of the present invention serving asreagents for oxidation reactions can be formed by graft-polymerizing4-vinylpyridine used as a polymerizable monomer onto an organic polymerbase such as a polyethylene nonwoven fabric via radiation-induced graftpolymerization to form a polymer side chain and then immersing the basein a solution containing dichromate or chlorochromate. Solid reagents ofthe present invention serving as reagents for oxidation reactions canalso be formed by immersing a graft base having graft-polymerized4-vinylpyridine in a solution containing an alkyl halide such as methyliodide to introduce a quaternary pyridinium-type anion exchange grouponto the polymer side chain on the base and converting the anion intohypochlorite ion, periodate ion, chromate ion, dichromate ion, etc.Solid reagents of the present invention serving as halogenating agentssuch as brominating agents can be formed by converting anion of thequaternary pyridinium-type anion exchange group introduced onto thepolymer side chain into bromide ion and then converting it intotribromide ion or the like.

Generally, conventional solid reagents based on polymer resin beads havereactive functional groups or reagent compound molecules immobilizedonto the backbone of a polymer resin to introduce functions as reagentsfor various reactions and polymer backbones are crosslinked to eachother to compensate for the physical strength deteriorated by theintroduction of these reactive functional groups or reagent compoundmolecules. In conventional solid reagents based on resin beads, variousreactive functional groups or reagent compound molecules are normallyintroduced onto the polymer chain obtained by polymerizing a monomersuch as styrene. However, they have the problem that the polymer chainis solvated with molecules of the solvent used for the reaction so thatit is swollen due to widened spaces between polymer chains and losesphysical strength to gel or dissolve in the solvent. Thus, a crosslinkersuch as divinylbenzene is added to crosslink polystyrene backbones eachother in order to solve this problem in conventional solid reagentsbased on resin beads. This increases physical strength of the resin, butcauses the problem that the formation of a crosslinked structure retardsthe diffusion speed of the starting compound or regenerant, resulting ina decline in reaction efficiency or regeneration efficiency. Especially,conventional solid reagents are based on porous resin beads and much ofthe reactive functional groups or reagent compound molecules introducedare also supported on the inner surfaces of micropores of the resin.When a starting compound is passed through a column packed with such asolid reagent to induce a reaction or a regenerant is passed through itto regenerate the reagent, the starting compound solution or regenerantsolution must be diffused deeply into micropores of the resin, whichoften causes the problem that the reactive functional groups or reagentcompound molecules supported on the reagent are not sufficientlyeffectively utilized. If one wishes to effectively carry out a reactionusing a conventional solid reagent, therefore, the starting compoundmust be passed extremely slowly to allow the starting compound to besufficiently diffused into micropores of the resin. Even if the startingmaterial solution is diffused into micropores of resin beads and reactswith reactive functional groups or reagent compound molecules to producea target compound, the resulting target compound must be diffused fromthe inside to the outside of the micropores at the recovery stage of theproduct, which often needs continuously passing the solution over a longperiod after the reaction to increase recovery. In contrast, solidreagents of the present invention made it possible to increase thediffusion speed of the starting compound or regenerant while keeping thephysical strength of the polymer backbone by locating a polymer sidechain on the polymer backbone of an uncrosslinked organic polymer baseand introducing a reactive functional group onto the polymer side chain.Thus, solid reagents of the present invention allow the reaction toproceed at a higher flow rate than previously, thereby increasing theprocess efficiency. Especially, solid reagents of the present inventionsucceeded in greatly improving reaction efficiency or regenerationefficiency because the polymer side chain has high mobility due to theabsence of crosslinked structure, thereby permitting easy access of thestarting compound or regenerant to any site of the polymer side chain atwhich the reactive functional group has been introduced as well aspermitting easy recovery of the product after the reaction. In solidreagents of the present invention, the backbone plays the role ofkeeping physical strength or configuration.

Solid reagents of the present invention can be used in e.g. a reactorcomprising a column 2 packed with a number of layers of a solid reagent1 in the form of a porous membrane or nonwoven fabric as shown inFIG. 1. A solution of a starting compound can be passed through thereactor where a desired reaction takes place to give a solution of atarget compound or a regenerant can be passed through the used column toregenerate the solid reagent. Alternatively, a solid reagent of thepresent invention in the form of a porous membrane or nonwoven fabriccan be wound into a roll 12 around a collecting tube 11 and packed in acolumn 13 to form a reactor as shown in FIG. 2, in which case a desiredreaction can be carried out or the used reagent can be regenerated bypassing a starting compound or a regenerant from the outside to theinside of roll 12.

Moreover, different kinds of solid reagents of the present invention canbe prepared and connected in series to achieve multistage syntheticreactions. As shown in FIG. 3, for example, a plurality of reactioncolumns 21, 22, 23 packed with solid reagents of the present inventionhaving different functions can be prepared and connected in series viaconnecting pipes 24 and 25 to supply a starting compound solution from amaterial feeding pipe 26 to first column 21, then successively column 22and column 23 for the subsequent reactions, whereby the final productcan be recovered from product recovery pipe 27. Thus, final product Dcan be obtained from starting material A via multistage syntheticreactions A→B→C→D, for example.

The present invention also relates to processes and apparatus forsynthesizing organic compounds as described above. Accordingly, otheraspects of the present invention relates to:

A process for synthesizing an organic compound, comprising bringing astarting compound into contact with a solid reagent of the presentinvention;

A multistage process for synthesizing an organic compound, comprisingpreparing a plurality of solid reagents of the present invention havingdifferent functions and successively bringing a starting compound intocontact with the plurality of solid reagents prepared;

An apparatus for synthesizing an organic compound, comprising a reactioncolumn packed with a solid reagent of the present invention; a materialfeeding section for feeding a starting compound to the reaction column;and a product recovery section for recovering the organic compoundproduced from the reaction column; and

A multistage apparatus for synthesizing an organic compound, comprisinga plurality of reaction columns packed with a plurality of solidreagents of the present invention having different functions; columnconnecting sections for connecting the plurality of reaction columns inseries; a material feeding section for feeding a starting compound tothe first one of the reaction columns connected in series; and a productrecovery section for recovering the organic compound produced from thelast reaction column.

According to the present invention, reagents participating in variousorganic synthetic reactions known in the art can be provided. Forexample, solid reagents of the present invention having hypochlorite orperiodate ion as a functional group can be used for oxidation reactionsin which an alcohol is oxidized to give an aldehyde or a ketone. Solidreagents of the present invention having tetrahydroborate ion as areactive functional group can be used for reduction reactions in whichan aldehyde or a ketone is reduced to give an alcohol. Solid reagents ofthe present invention having a halide ion such as fluoride ion or atrihalide ion such as tribromide ion as a functional group can be usedas halogenating agents in various halogenation reactions.

EXAMPLES

The following examples further illustrate the present invention. Theseexamples are given only for illustrating some embodiments of the presentinvention, but are not construed to limit the invention thereto.

Example 1 Preparation of a Solid Reagent

A nonwoven fabric base made of polyethylene fibers (fiber diameter 20-30μm; areal density 50-60 g/m²; available from Japan Vilene Co., Ltd.under product code OX-8901T6) in an amount of 20.8 g was irradiated withγ-rays at 160 kGy with cooling on dry ice. This irradiated base wasimmersed in chloromethylstyrene (50% m-isomer, 50% p-isomer, availablefrom Seimi Chemical Co., Ltd. under trade name CMS-AM) preliminarilyfreed of polymerization inhibitors and underwent a graft polymerizationreaction at 60° C. for 3 hours. The nonwoven fabric was removed andsuccessively washed with toluene and acetone and wiped and then dried at40° C. at normal pressure for 12 hours to give 45.5 g of achloromethylstyrene-grafted nonwoven fabric having a grafting degree of119%.

This grafted nonwoven fabric in an amount of 27.3 g was immersed in amixed solution of a 30% aqueous trimethylamine solution (90 mL, 433mmol) and pure water (400 mL) and stirred at 50° C. for 2 days. Thenonwoven fabric was removed and successively washed with pure water, 0.1N hydrochloric acid and pure water and wiped, and then dried at 60° C.at normal pressure for 12 hours to give 32.9 g of an anion exchangenonwoven fabric having an anion exchange capacity of 2.75 mmol/g-R(/g-R: per g material).

The anion exchange nonwoven fabric obtained as above (32.9 g) wasimmersed in a solution of sodium bromide (92.7 g, 433 mmol) dissolved inpure water (400 mL) and stirred at room temperature for 2 hours. Thereaction solution was discarded and the same aqueous sodium bromidesolution as above was added again and stirred for 6 hours. The nonwovenfabric was removed and washed three times with pure water (500 mL) andwiped, and then dried at 60° C. at normal pressure for 12 hours to givea Br⁻-type anion exchange nonwoven fabric.

Thus obtained Br⁻-type anion exchange nonwoven fabric (11.8 g) wasimmersed in a solution of bromine (3.7 g, 23.3 mmol) in dichloromethane(500 mL) and stirred at room temperature for 12 hours. After thereaction solution was discarded, the nonwoven fabric was washed threetimes with dichloromethane (500 mL) and wiped, and then dried at 40° C.at normal pressure for 2 hours to give 15.4 g of solid reagent Aaccording to the present invention in the form of an orange nonwovenfabric. Thus obtained solid reagent A had a functional group content of1.95 mmol/g-R.

Comparative Example 1 Preparation of a Conventional Solid Reagent Basedon Resin Beads

Br⁻-type porous anion exchange resin beads (available from Sigma-Aldrichunder product code 51,376-8) in an amount of 10 g were immersed in asolution of bromine (5.6 g, 35 mmol) in dichloromethane (200 mL) andshaken at room temperature for 12 hours. The reaction mixture wasfiltered and the resin was washed with dichloromethane, and then driedat 40° C. for 12 hours to give 15.2 g of solid reagent B in the form oforange porous resin beads. Thus obtained solid reagent B had afunctional group content of 2.3 mmol/g-R and a particle diameter of0.4-0.6 mm.

Example 2 Synthesis of 2,6-dibromo-4-methylphenol with Solid Reagent A

Round sections of 18 mm in diameter of solid reagent A were packed at aheight of 50 mm in a glass column of 18 mm in inner diameter containingdichloromethane with caution to prevent air bubbles from entering thecolumn (a total of 58 sections packed). The amount of solid reagent Apacked was 3.85 g (functional group content=7.5 mmol). This column waspretreated by passing 40 mL of a dichloromethane-methanol mixed solvent(volume ratio=5:2) at a flow rate of 10 mL/min. Then, 50 mL of asolution of p-cresol in a dichloromethane-methanol mixed solvent (volumeratio=5:2) was passed using a feed pump at a given flow rate, and then adichloromethane-methanol mixed solvent (volume ratio=5:2) was passed.

After starting to pass the p-cresol solution, a first 100 mL aliquot ofeffluent was concentrated under reduced pressure and combined with a 5%aqueous sodium bisulfite solution (50 mL) and extracted three times withdiethyl ether (40 mL). The extract was dried over magnesium sulfate andthen concentrated under reduced pressure and further concentrated via avacuum pump. The residue was combined with an internal standardtetrachloroethane (671.4 mg, 4.0 mmol) and diluted in deuteratedchloroform for ¹H-NMR analysis to determine the recovery percentages ofp-cresol, 2-bromo-4-methylphenol and 2,6-dibromo-4-methylphenol. Theresults are shown in Table 1.

TABLE 1 Results of Example 2 Concentration of p-cresol 80 40 40 40solution (mmol/L) Amount of p-cresol added 4.0 2.0 2.0 2.0 (mmol) Amountof p-cresol relative to 0.53 0.27 0.27 0.27 solid reagent (equivalent)Flow rate (mL/min) 10.0 10.0 4.0 1.5 Recovery (%) p-cresol 24 0 0 02-bromo-4- 51 48 20 0 methylphenol 2,6-dibromo-4- 17 50 78 99methylphenol Total 92 98 98 99

Comparative Example 2

Synthesis of 2,6-dibromo-4-methylphenol with Solid Reagent B

Solid reagent B was packed at a height of 50 mm in a glass column of 18mm in inner diameter containing dichloromethane with caution to preventair bubbles from entering between beads. A round polyethylene nonwovenfabric of 18 mm in diameter and glass beads (1.5-2.5 mm in diameter)were overlaid in a height of 20 mm. The amount of solid reagent B packedwas 7.1 g (functional group content 16.3 mmol). Then, a solution ofp-cresol in dichloromethane-methanol was passed and the recoverypercentage of each compound in 100 mL of effluent was determined from¹H-NMR in the same manner as in Example 2. The results are shown inTable 2.

TABLE 2 Results of Comparative example 2 Concentration of p-cresol 80 4040 40 solution (mmol/L) Amount of p-cresol added 4.0 2.0 2.0 2.0 (mmol)Amount of p-cresol relative to 0.24 0.12 0.12 0.12 solid reagent(equivalent) Flow rate (mL/min) 10.0 10.0 4.0 1.5 Recovery (%) p-cresol2 2 0 0 2-bromo-4- 52 58 31 7 methylphenol 2,6-dibromo-4- 0 2 50 88methylphenol Total 54 62 81 95

The results of Table 1 and Table 2 show that solid reagent A accordingto the present invention was superior in reactivity as a solid reagentdespite the lower functional group content. Especially, it is shown thatthe target compound 2,6-dibromo-4-methylphenol was obtained at a veryhigh yield of approximately 100% when solid reagent A was used under alow flow rate condition at 1.5 mL/min. Comparison of the results ofsolid reagent A and solid reagent B under the same conditions revealsthat solid reagent A is superior in both of the yield of the targetcompound and the total recovery of whole compounds. This shows thatsolid reagent A based on a nonwoven fabric according to the presentinvention virtually eliminates the necessity for a larger amount ofsolvent or a lower flow rate in contrast to solid reagent B in the formof porous resin beads in which the starting material solution oncediffused into micropores of the resin must be diffused again to theoutside of the micropores in order to flow out from the column.

Example 3 Preparation of a Solid Reagent

The anion exchange nonwoven fabric obtained in Example 1 (6.83 g) wasimmersed in an aqueous 0.5% sodium boron hydride solution (200 mL) andstirred at room temperature for 1 hour in a glass ampule. The nonwovenfabric was removed and successively washed with pure water and methanoland wiped, and then dried at 50° C. for 6 hours to give 6.50 g of solidreagent C according to the present invention in the form of a whitenonwoven fabric. The reduction capacity of solid reagent C determined byreaction with an excess amount of benzaldehyde was 6.96 meq/g-R.Supposing that 4 equivalents of hydride ion (H⁺) can be released from 1equivalent of BH₄ ⁻ion, the functional group content of BH₄ ⁻is 1.74mmol/g-R.

Example 4 Reduction of Benzaldehyde with Solid Reagent C

In the same manner as in Example 2, disc-like sections (φ 18 mm, 2.54cm²) of solid reagent C were packed in a glass column of 18 mm in innerdiameter (h=28 mm, Vol.=7.3 mL, reduction capacity=6.4 mmol) andoverlaid with glass beads. Thus formed liquid pass experimentalapparatus is filled with ethanol and degassed, and then conditioned withethanol. A solution of 1.6 mmol benzaldehyde in ethanol (50 mL) and thenethanol were passed. A first 100 mL aliquot of effluent was concentratedunder reduced pressure and further concentrated via a vacuum pump. Theresidue was weighed and diluted in deuterated chloroform for ¹H-NMRanalysis to determine the recovery percentages of benzaldehyde andbenzyl alcohol. The results are shown in Table 3.

TABLE 3 Results of Example 4 Equivalent of the reducing agent 4.0 4.04.0 relative to benzaldehyde Flow rate (mL/min) 10.0 5.0 2.0 Recovery(%) Benzaldehyde 16 4 0 Benzyl alcohol 78 81 84 Total 94 85 84

Comparative Example 3 Preparation of a Conventional Solid Reagent Basedon Resin Beads

Cl⁻-type porous anion exchange resin beads (available from Rohm & Haasunder trade name Amberlite IRA900J) in an amount of 5.0 g were immersedin an aqueous 0.5% sodium boron hydride solution (200 mL) and shaken atroom temperature for 1 hour. The reaction mixture was filtered and theresin was washed with pure water, and then dried at 50° C. for 3 hoursto give 4.9 g of solid reagent D in the form of white porous beads. Thusobtained solid reagent D had a reduction capacity of 9.76 meq/g-R asdetermined in the same manner as in Example 3.

Comparative example 4 Reduction of Benzaldehyde with Solid Reagent D

Solid reagent D was packed in a glass column of 18 mm in inner diametercontaining ethanol (h=9 mm, Vol.=2.3 mL, reduction capacity=6.4 mmol)with caution to prevent air bubbles from entering the column. A roundpolyethylene nonwoven fabric of 18 mm in diameter and glass beads wereoverlaid with caution to prevent air bubbles from entering the column.Then, the column was conditioned with ethanol and a solution of 1.6 mmolbenzaldehyde in ethanol (50 mL) was passed, after which the recoverypercentages of benzaldehyde and benzyl alcohol were determined from¹H-NMR in the same manner as in Example 4. Similar experiments wereperformed with an increased amount of solid reagent D (h=28 mm, Vol.=7.3mL, reduction capacity=19.2 mmol). The results are shown in Table 4.

TABLE 4 Results of Comparative example 4 Equivalent of the reducingagent 4.0 12.0 12.0 relative to benzaldehyde Flow rate (mL/min) 10.010.0 2.0 Recovery (%) Benzaldehyde 83 56 14 Benzyl alcohol 13 16 41Total 96 72 55

The results of Table 3 and Table 4 also show that solid reagent Caccording to the present invention afforded the target compound benzylalcohol with higher yields even at higher flow rates and lowerfunctional group contents, demonstrating that it is superior inreactivity as a solid reagent.

Advantages of the Invention

According to the present invention, solid reagents having very excellentreaction efficiency as compared with conventional solid reagents basedon resin beads are provided. Solid reagents according to the presentinvention are useful in various organic synthetic reactions. Solidreagents according to the present invention can achieve very highutilization efficiency of functional groups carried thereon bycontrolling the flow rate of the starting material. Therefore, theamount of the solid reagent packed in a reaction column (functionalgroup content) can be smaller than previously and desired compounds canbe obtained with higher yield than previously.

1. A solid reagent comprising an organic polymer base in which a graftpolymer side chain is introduced onto the backbone of the organicpolymer base, wherein the graft polymer side chain has a formula (I):

wherein, n is an integral equal to two or more, X is a reactivefunctional group selected from the group consisting of hypochlorite ion,periodate ion, peroxide ion, chromate ion, dichromate ion, perruthenateion, tetrahydroborate ion, cyanotrihydroborate ion, tribromide ion,cyanide ion, thiocyanate ion, azide ion and nitrite ion.
 2. A solidreagent comprising an organic polymer base in which a graft polymer sidechain is introduced onto the backbone of the organic polymer base,wherein the graft polymer side chain has a formula (II):

wherein, n is an integral equal to two or more, X is a reactivefunctional group selected from the group consisting of hypochlorite ion,periodate ion, peroxide ion, chromate ion, dichromate ion, perruthenateion, tetrahydroborate ion, cyanotrihydroborate ion, tribromide ion,cyanide ion, thiocyanate ion, azide ion and nitrite ion.
 3. The solidreagent of claim 1 wherein the organic polymer base is in the form of afiber, a woven or nonwoven fabric consisting of an assembly of fibers, aporous membrane or a hollow fiber membrane.
 4. The solid reagent ofclaim 1 wherein the graft polymer side chain is introduced via aradiation-induced graft polymerization.
 5. The solid reagent of claim 1wherein the reactive functional group serves as a reagent for any one ofoxidation reaction, reduction reaction, halogenation reaction ornucleophilic replacement reaction.
 6. A process for preparing a solidreagent of claim 1, comprising: graft-polymerizing chloromethylstyreneonto the backbone of an organic polymer base to form a graft polymerside chain; introducing a quaternary ammonia-type anion exchange grouponto the graft polymer side chain to form a graft polymer side chainhaving the anion exchange group; and contacting the graft polymer sidechain having the quaternary ammonia-type anion exchange group with asolution containing a reactive functional group selected from the groupconsisting of hypochlorite ion, periodate ion, peroxide ion, chromateion, dichromate ion, perruthenate ion, tetrahydroborate ion,cyanotrihydroborate ion, tribromide ion, cyanide ion, thiocyanate ion,azide ion and nitrite ion to convert a counter anion attached to theanion exchange group into the reactive functional group.
 7. The solidreagent of claim 3 wherein the graft polymer side chain is introducedvia a radiation-induced graft polymerization.
 8. The solid reagent ofclaim 3 wherein the reactive functional group serves as a reagent forany one of oxidation reaction, reduction reaction, halogenation reactionor nucleophilic replacement reaction.
 9. The solid reagent of claim 4wherein the reactive functional group serves as a reagent for any one ofoxidation reaction, reduction reaction, halogenation reaction ornucleophilic replacement reaction.
 10. A process for preparing a solidreagent of claim 3, comprising: graft-polymerizing chloromethylstyreneonto the backbone of an organic polymer base to form a graft polymerside chain; introducing a quaternary ammonia-type anion exchange grouponto the graft polymer side chain to form a graft polymer side chainhaving the anion exchange group; and contacting the graft polymer sidechain having the quaternary ammonia-type anion exchange group with asolution containing a reactive functional group selected from the groupconsisting of hypochlorite ion, periodate ion, peroxide ion, chromateion, dichromate ion, perruthenate ion, tetrahydroborate ion,cyanotrihydroborate ion, tribromide ion, cyanide ion, thiocyanate ion,azide ion and nitrite ion to convert a counter anion attached to theanion exchange group into the reactive functional group.
 11. A processfor preparing a solid reagent of claim 4, comprising: graft-polymerizingchloromethylstyrene onto the backbone of an organic polymer base to forma graft polymer side chain; introducing a quaternary ammonia-type anionexchange group onto the graft polymer side chain to form a graft polymerside chain having the anion exchange group; and contacting the graftpolymer side chain having the quaternary ammonia-type anion exchangegroup with a solution containing a reactive functional group selectedfrom the group consisting of hypochlorite ion, periodate ion, peroxideion, chromate ion, dichromate ion, perruthenate ion, tetrahydroborateion, cyanotrihydroborate ion, tribromide ion, cyanide ion, thiocyanateion, azide ion and nitrite ion to convert a counter anion attached tothe anion exchange group into the reactive functional group.
 12. Aprocess for preparing a solid reagent of claim 5, comprising:graft-polymerizing chloromethylstyrene onto the backbone of an organicpolymer base to form a graft polymer side chain; introducing aquaternary ammonia-type anion exchange group onto the graft polymer sidechain to form a graft polymer side chain having the anion exchangegroup; and contacting the graft polymer side chain having the quaternaryammonia-type anion exchange group with a solution containing a reactivefunctional group selected from the group consisting of hypochlorite ion,periodate ion, peroxide ion, chromate ion, dichromate ion, perruthenateion, tetrahydroborate ion, cyanotrihydroborate ion, tribromide ion,cyanide ion, thiocyanate ion, azide ion and nitrite ion to convert acounter anion attached to the anion exchange group into the reactivefunctional group.
 13. The process of claim 6 wherein the graftpolymerization is conducted via a radiation-induced graftpolymerization.
 14. The solid reagent of claim 2 wherein the organicpolymer base is in the form of a fiber, a woven or nonwoven fabricconsisting of an assembly of fibers, a porous membrane or a hollow fibermembrane.
 15. The solid reagent of claim 2 wherein the graft polymerside chain is introduced via a radiation-induced graft polymerization.16. The solid reagent of claim 2 wherein the reactive functional groupserves as a reagent for any one of oxidation reaction, reductionreaction, halogenation reaction or nucleophilic replacement reaction.17. A process for preparing a solid reagent of claim 2, comprising:graft-polymerizing 4-vinylpyridine onto the backbone of an organicpolymer base to form a graft polymer side chain; introducing aquaternary pyridinium-type anion exchange group onto the graft polymerside chain to form a graft polymer side chain having the anion exchangegroup: and contacting the graft polymer side chain having the quaternarypyridinium-type anion exchange group with a solution containing areactive functional group selected from the group consisting ofhypochlorite ion, periodate ion, peroxide ion, chromate ion, dichromateion, perruthenate ion, tetrahydroborate ion, cyanotrihydroborate ion,tribromide ion, cyanide ion, thiocyanate ion, azide ion and nitrite ionto convert a counter anion attached to the anion exchange group into thereactive functional group.
 18. The solid reagent of claim 14 wherein thegraft polymer side chain is introduced via a radiation-induced graftpolymerization.
 19. The solid reagent of claim 14 wherein the reactivefunctional group serves as a reagent for any one of oxidation reaction,reduction reaction, halogenation reaction or nucleophilic replacementreaction.
 20. The solid reagent of claim 15 wherein the reactivefunctional group serves as a reagent for any one of oxidation reaction,reduction reaction, halogenation reaction or nucleophilic replacementreaction.
 21. A process for preparing a solid reagent of claim 14,comprising: graft-polymerizing 4-vinylpyridine onto the backbone of anorganic polymer base to form a graft polymer side chain; introducing aquaternary pyridinium-type anion exchange group onto the graft polymerside chain to form a graft polymer side chain having the anion exchangegroup; and contacting the graft polymer side chain having the quaternarypyridinium-type anion exchange group with a solution containing areactive functional group selected from the group consisting ofhypochlorite ion, periodate ion, peroxide ion, chromate ion, dichromateion, perruthenate ion, tetrahydroborate ion, cyanotrihydroborate ion,tribromide ion, cyanide ion, thiocyanate ion, azide ion and nitrite ionto convert a counter anion attached to the anion exchange group into thereactive functional group.
 22. A process for preparing a solid reagentof claim 15, comprising: graft-polymerizing 4-vinylpyridine onto thebackbone of an organic polymer base to form a graft polymer side chain;introducing a quaternary pyridinium-type anion exchange group onto thegraft polymer side chain to form a graft polymer side chain having theanion exchange group; and contacting the graft polymer side chain havingthe quaternary pyridinium-type anion exchange group with a solutioncontaining a reactive functional group selected from the groupconsisting of hypochlorite ion, periodate ion, peroxide ion, chromateion, dichromate ion, perruthenate ion, tetrahydroborate ion,cyanotrihydroborate ion, tribromide ion, cyanide ion, thiocyanate ion,azide ion and nitrite ion to convert a counter anion attached to theanion exchange group into the reactive functional group.
 23. A processfor preparing a solid reagent of claim 16, comprising:graft-polymerizing 4-vinylpyridine onto the backbone of an organicpolymer base to form a graft polymer side chain; introducing aquaternary pyridinium-type anion exchange group onto the graft polymerside chain to form a graft polymer side chain having the anion exchangegroup; and contacting the graft polymer side chain having the quaternarypyridinium-type anion exchange group with a solution containing areactive functional group selected from the group consisting ofhypochlorite ion, periodate ion, peroxide ion, chromate ion, dichromateion, perruthenate ion, tetrahydroborate ion, cyanotrihydroborate ion,tribromide ion, cyanide ion, thiocyanate ion, azide ion and nitrite ionto convert a counter anion attached to the anion exchange group into thereactive functional group.
 24. The process of claim 17 wherein the graftpolymerization is conducted via a radiation-induced graftpolymerization.